Geminal-dinitro-1-5 diazocine derivatives

ABSTRACT

This invention involves a new class of compounds, certain geminal-dinitro-substituted heterocycles, including geminal-bis(difluoramino)-substituted heterocyclic nitramines and the production thereof. More specifically, this invention involves the production of 3,3-bis(difluoramino)octahydro-1,5,7,7-tetranitro-1,5-diazocine (TNFX), which may be formulated into explosives and propellant oxidizers. The method of making a 3,3-bis(difluoramino)octahydro-1,5,7,7-tetranitro-1,5-diazocine comprises reacting a hexahydro-7,7-dinitro-1,5-bis(nitrobenzenesulfonyl)-1,5-diazocin-3(2 H)-one with a difluoramine source to produce a 3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(nitrobenzenesulfonyl)-1,5-diazocine and reacting said 3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(nitrobenzenesulfonyl)-1,5-diazocine with a highly reactive nitrating reagent in the presence of a strong Lewis acid, such as antimony pentafluoride, boron triflate or boron fluorosulfonate.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is being filed as a Divisional Application inaccordance with 37 C.F.R. 1.53(b). The Parent Application of thisDivisional Application is application Ser. No. 09/835,783 filed Apr. 11,2001 now U.S. Pat. No. 6,417,355.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention involves a new class of compounds,geminal-bis(difluoramino)-substituted heterocyclic nitramines, and theproduction thereof. More specifically, this invention involves theproduction of 3,3-bis(difluoramino)octahydro-1,5,7,7-tetranitro-1,5-diazocine (TNFX),which may be formulated into explosives and pro pellant oxidizers.

2. Description of the Related Art

The synthesis of certain examples of this class of compounds,geminal-bis(difluoramino)-substituted heterocyclic nitramines, isdifficult and nonintuitive. The certain examples that are particularlysynthetically difficult are molecules that incorporate thegeminal-bis(difluoramino)alkylene [C(NF₂)₂] component and the nitraminecomponent [N—NO₂] in close proximity, especially when separated by onlya methylene (CH₂) link in order to maintain a low fuel-to-oxidizercomponent ratio and con comitantly high oxygen balance in the productmolecule. This invention involves3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-diazocine derivatives (aheretofore unknown specific class of compound) and novel precursors tothese new derivatives, by the use of certain key intermediates andreagents which allow formation of this target structural subcomponent.

The calculated performance improvements expected fromgeminal-bis(difluoramino)-substituted heterocyclic nitramines whenformulated into explosives and propellants has been reported. [Miller,Materials Research Society Proceedings 1996, 418, 3].

Methodology for preparing a geminal-bis(difluoramino)-substitutednitrogenous heterocycle has been reported in Chapman et al. Journal ofOrganic Chemistry 1998, 63, 1566, incorporated herein by reference, whodescribe the preparation of 3,3,7,7-tetrakis(difluoramino) octahydro-1,5-bis(4-nitrobenzenesulfonyl)-1,5-diazocine; this intermediate wasconverted to the corresponding nitramine, 3,3,7,7-tetrakis(difluoramino)octahydro-1,5-dinitro-1,5-diazocine, given the acronym HNFX as discussedin Chapman et al, Journal of Organic Chemistry 1999, 64, 960,incorporated herein by reference.

Methodology for preparing a structurally similargeminal-dinitro-substituted nitrogenous heterocycle has been reported byCichra and Adolph [Synthesis 1983, 830], who describe the preparation ofoctahydro-1,3,3,5,7,7-hexanitro-1,5-diazocine.

However, the preparation of asymmetric octahydro -1,5-diazocinederivatives incorporating both geminal-dinitro andgeminal-bis(difluoramino) substituents has not been previouslydescribed. A particularly attractive target compound in terms ofproviding this asymmetric functionality would be3,3-bis(difluoramino)octahydro-1,5,7,7-tetranitro-1,5-diazocine, givenby us the acronym TNFX by analogy to the acronyms HNFX and RNFX. Theincorporation of both functionalities provides a difluoramino componentdesired for energetic combustion of metallized-fuel propellantformulations, and the gem-dinitro component provides higher oxygenbalance (for more-complete combustion) than analogous all-difluoraminoderivatives.

SUMMARY OF THE INVENTION

The present invention relates to3,3-bis(difluoramino)octahydro-1,5,7,7-tetranitro -1,5-diazocine (TNFX)and precursors leading to TNFX and provides a process for thepreparation of TNFX having the formula:

A preferred embodiment of the present invention relates to methods forthe preparation of certain new geminal-dinitro-1,5-diazocine derivativeswhich are suitable precursors leading to TNFX. The invention alsoinvolves novel and nonintuitive methods for the preparation of TNFX, aspecific member of a general class of compounds with the substructure3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-diazocine. TNFX isproduced by the use of intermediates which allow formation of the targetstructural subcomponents, octahydro-3,3-dinitro-1,5-diazocine and a morespecific substructure of3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-diazocine.

In a preferred embodiment of the present invention, the substitution onheterocyclic precursors' nitrogen atoms is significant. The nitrogenatoms of heterocyclic precursors (such as diazocines) must be suitablysubstituted, or “protected,” during the process of difluoramination toallow this process to proceed to geminal-bis(difluoramino)alkylenederivatives. Without suitable protection of proximate multiplenitrogens, especially those separated from reacting carbonyl sites by ashort bridge, such as methylene, the process of difluoramination ofketone intermediates does not proceed togeminal-bis(difluoramino)alkylene derivatives. The result ismono(difluoramino) alkylene derivatives or no reaction at all.

In a preferred embodiment of the present invention, the method of makinga 3,3-bis(difluoramino)octahydro -1,5,7,7-tetranitro-1,5-diazocinecomprises reacting ahexahydro-7,7-dinitro-1,5-bis(nitrobenzenesulfonyl)-1,5-diazocin-3(2H)-onewith a difluoramine source to produce a3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(nitrobenzenesulfonyl)-1,5-diazocineand reacting said3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(nitrobenzenesulfonyl)-1,5-diazocinewith a highly reactive nitrating reagent in the presence of a strongLewis acid, such as antimony pentafluoride, boron triflate or boronfluorosulfonate.

An object of a preferred embodiment of the present invention is tocreate a novel explosive and propellant oxidizer involvinggeminal-bis(difluoramino)-substituted heterocyclic nitramines.

Another object of a preferred embodiment of the present invention is toprovide a method of producing3,3-bis(difluoramino)octahydro-1,5,7,7-tetranitro-1,5-diazocine (TNFX).

Yet another objective of object of a preferred embodiment of the presentinvention is provide a method of producing TFNX in appreciable yield byremoving the electron withdrawing nitrobenzene sulfonyl nitrogenprotecting groups on3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(nitrobenzenesulfonyl)-1,5-diazocinewith sufficiently reactive nitrating reagent.

BRIEF DESCRIPTION DRAWINGS

FIG. 1 is a diagram of a general reaction path of a preferred embodimentof the present invention, which details the diazine intermediates.

FIG. 2 is a diagram of the a general reaction path of a preferredembodiment of the present invention, which details the steps forconversion ofhexahydro-7,7-dinitro-1,5-bis(2-nitrobenzenesulfonyl)-1,5-diazocin-3(2H)-oneto TNFX.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to3,3-bis(difluoramino)octahydro-1,5,7,7-tetranitro-1,5-diazocine(TNFX)and provides a process for the preparation of TNFX having theformula:

A preferred embodiment of the process of the present invention utilizesdiazocine intermediates, which are suitable for eventual conversion toTNFX. The reaction path of a preferred embodiment of the presentinvention, generally, is described in FIG. 1. In FIG. 1, the % yield isthe experimental % yield of 2A through 9A and 2B through 9B,

2A through 9A represents the experimental results where Ns is o-nosyl

derivative and

2B through 9B represents the experimental results where Ns is p-nosyl

derivative respectively.

In addition to o-nosyl and p-nosyl, the sulfonyl substituents, Ns, mayinclude alkanesulfonyl, halosulfonyl, or arenesulfonyl substituents, butthe arenesulfonyl must have electron-withdrawing subsitituents on thephenyl rings. For example, the nitro group (NO₂) is a suitableelectron-withdrawing subsitituent. Any single or multipleelectron-withdrawing subsitituent(s) that collectively lower(s) thebasicity of the arenesulfonyl-protected nitrogens below that of theoxygen will be suitable. Similarly, alkanesulfonyl protecting groups maybe electronegatively substituted to impart the same property on theprotected nitrogens. In general, the sulfonyl substituent must have aninductive substituent constant (σ₁ or F) of a value greater than that ofunsubstituted benzenesulfonyl, approximately 0.58. Examples ofpreferable sulfonyl substituents are halosulfonyl, any regioisomer offluoroarenesulfonyl, such as 2-,3- and 4-fluoro-substitutedarenesulfonyl, polyhaloalkanesulfonyl, polyhaloarenesulfonyl, anyregioisomer of cyanoarenesulfonyl, such as 2-,3- and 4-cyano-substitutedarenesulfonyl, polycyanoarenesulfonyl, any regioisomer ofnitroarenesulfonyl, such as 2-,3- and 4-nitro-substituted arenesulfonyland polynitroarenesulfonyl.

The synthetic sequence leading to TNFX involves substitution onheterocyclic precursors' nitrogen atoms. The nitrogen atoms ofheterocyclic precursors (such as diazocines) must be suitablysubstituted, or “protected,” during the process of difluoramination toallow this process to proceed to geminal-bis(difluoramino)alkylenederivatives. Without suitable protection of proximate multiplenitrogens, especially those separated from reacting carbonyl sites by ashort bridge, such as methylene, the process of difluoramination ofketone intermediates does not proceed togeminal-bis(difluoramino)alkylene derivatives. A preferred embodiment ofthe present invention is illustrated in FIG. 2.

In addition to the preferred p-nosyl substituent illustrated aboveseveral other sulfonyl subsitituents may be utilized. The sulfonylsubstituents may include alkanesulfonyl, halosulfonyl, or arenesulfonylsubstituents, but the arenesulfonyl must have electron-withdrawingsubsitituents on the phenyl rings. For example, the nitro group (NO₂) isa suitable electron-withdrawing subsitituent. Any single or multipleelectron-withdrawing subsitituent(s) that collectively lower(s) thebasicity of the arenesulfonyl-protected nitrogens below that of theoxygen will be suitable. Similarly, alkanesulfonyl protecting groups maybe electronegatively substituted to impart the same property on theprotected nitrogens. In general, the sulfonyl substituent must have aninductive substituent constant (σ₁ or F) of a value greater than that ofunsubstituted benzenesulfonyl, approximately 0.58. Examples ofpreferable sulfonyl substituents are halosulfonyl, any regioisomer offluoroarenesulfonyl, such as 2-,3- and 4-fluoro-substitutedarenesulfonyl, polyhaloalkanesulfonyl, polyhaloarenesulfonyl, anyregioisomer of cyanoarenesulfonyl, such as 2-,3- and 4-cyano-substitutedarenesulfonyl, polycyanoarenesulfonyl, any regioisomer ofnitroarenesulfonyl, such as 2-,3- and 4-nitro-substituted arenesulfonyland polynitroarenesulfonyl.

The synthetic sequence leading to TNFX is continued from theintermediates detailed in Scheme 1, especially the immediately previousintermediate, hexahydro-7,7-dinitro-1,5-bis(nitrobenzenesulfonyl)-1,5-diazocin-3(2H)-one, bytransformations effecting difluoramination of the carbonyl group (i.e.,conversion to a gem-bis(difluoramino)alkylene component), which isaccomplished by conversion of the ketone carbonyl group in a reactionwith difluoramine or difluorosulfamic acid in the presence of a strongacid acid such as sulfuric acid (including fuming sulfuric acid). Thesubsequent (sequent) nitrolyses of the nitrobenzenesulfonyl N-protectinggroups in order to prepare the corresponding bisnitramine, TNFX, asshown in Scheme 2 above.

The latter steps of the sequence (i.e., the N-nitrolyses) areparticularly difficult, and the successful conditions leading tonitrolysis to the bisnitramine (TNFX) are particularly novel andnonintuitive, due to the highly deactivating nature of the numerouselectron-withdrawing and sterically hindering groups attached to thenitrolyzed nitrogens. The adverse effects of electron-withdrawing andsterically hindering groups on susceptibility of protected nitrogens toN-nitrolysis have been previously reviewed by Chapman et al. Journal ofOrganic Chemistry 1999, 64, 960, incorporated herein by reference. Inhighly deactivated amides (N-protected amines), such as suitableprecursors to HNFX and TNFX, N-nitrolysis requires the use of a highlyreactive nitrating reagent such as protonitronium (NO₂H₂ ⁺), formed viaprotonation of a nitronium (NO₂ ⁺) source in a very strong acid, i.e., asuperacid. The highly reactive nitrating reagent protonitronium (NO₂H₂⁺) is more efficiently formed in systems combining a superacid with astrong Lewis acid, in order to increase the acidity of the system. Thesystem trifluoromethanesulfonic acid-antimony pentafluoride is used in apreferred embodiment of the present invention. Other examples ofsuperacid systems suitable for formation of protonitronium may utilizeother perfluoroalkanesulfonic acids, fluorosulfonic acid, or hydrogenfluoride in the presence of certain Lewis acids. Other Lewis acids whichmay be suitable for forming protonitronium in combination withsuperacids include a variety of halides and pseudohalides of main groupelements and of certain transition metals such as tantalum. Theformation of protonitronium in other superacid systems has beendescribed by Olah et al., Journal of Organic Chemistry 1995, 60, 7348,who use the superacid system trifluoromethanesulfonic acid-triflatoboricacid. In the present preparation of TNFX, the cumulative deactivatingeffects of electronegative and bulky β,β-bis(difluoramino)alkyl andβ,β-dinitroalkyl substituents on the diazocine nitro gens (imparting apseudoneopentyl steric environment to them), and theelectron-withdrawing nitrobenzenesulfonyl N-protecting groups, renderedthe intermediate 3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(nitrobenzenesulfonyl)-1,5-diazocine resistant tonitrolysis even by the strong nitrating system nitricacid-trifluoromethanesulfonic acid, as had been successfully used forprevious preparations of HNFX. A modification of the nitrating systemwas required in order to generate sufficient protonitronium ion (insitu) to effect N-nitrolysis of the nitrobenzenesulfonyl protectinggroups and generate the desired TNFX in appreciable yield. Thus, theaddition of a strong Lewis acid to the system with nitricacid-trifluoromethanesulfonic acid rendered the nitrating reagentsufficiently reactive to remove both N-protecting groups underappropriate conditions to generate TNFX. In a preferred embodiment ofthe present invention, the strong Lewis acid antimony pentafluoride isused, but other Lewis acids such as boron triflate or boronfluorosulfonate may be utilized.

Further, the use of para-nitrobenzenesulfonyl-protected diazocines isshown as a preferred embodiment in Scheme 2. The use ofortho-nitrobenzenesulfonyl-protected diazocines produced desirednitramine(s) in only low (though detectable) yield, tentatively due tocompeting C-nitration at the initially unsubstituted para positions ofortho-nitrobenzenesulfonyl protecting groups. Resultant2,4-dinitrobenzenesulfonyl protecting groups are subsequently much moredifficult to remove than mononitrobenzenesulfonyl protecting groups, andTNFX is formed only to a small extent by successful competition ofN-nitrolysis of two ortho-nitrobenzenesulfonyl protecting groups againstC-nitration of the para position(s) of protecting groups.

The most desirable product, TNFX, exhibits further attractive attributesin addition to its combination of difluoramino and C-nitro substituents.Samples of TNFX have exhibited the property of crystal polymorphism, asdetermined by X-ray diffraction analysis. Thus, one polymorph of TNFXshows a higher density than the single crystal form of HNFX that hasbeen observed to date, proving that polymorphism in3,3,7,7-tetrasubstituted octahydro-1,5-dinitro-1,5-diazocines is afeasible phenomenon to induce, as had been computationally predicted forHNFX though not yet experimentally observed.

EXAMPLES Example 1 Preparation ofhexahydro-7,7-dinitro-1,5-bis(4-nitrobenzenesulfonyl)-1,5-diazocin-3(2H)-oneethylene ketal (“Ns”=p-nitrobenzenesulfonyl)

To a stirred solution of 1 (5.30 g, 58.8 mmole) and potassium carbonate(21.54 g, 155.8 mmole) in water (100 mL) maintained at 0° C. was addedp-nosyl chloride (29.27 g, 132.1 mmole) in THF (60 mL) dropwise. Uponcompletion of the addition, the reaction mixture was stirred at roomtemperature overnight and then concentrated under reduced pressure toremove THF. The solid was filtered. After washed with water, methylenechloride and dried, compound 2a was afforded as a pale yellow solid(25.57 g, 95%); 2a was chromatographed on silica gel eluting with ethylacetate/hexanes (1:1). Removal of solvent and recrystallization fromacetone and hexanes gave a colorless crystalline solid: mp 210-212° C.(sub.). ¹H NMR (acetone-d₆): δ2.96 (m, 2 H), 3.11 (m, 2 H), 3.78 (m, 1H), 4.40 (d, J=5.49 Hz, 1 H), 6.89 (t, 2 H), 8.11 (d, J=9.16 Hz, 4 H),8.42 (d, J=9.15, 4 H). ¹³C NMR (acetone-d₆): δ47.4, 69.8, 125.2, 129.2,147.5, 151.0. MS (CI/NH₃): m/z 478 (M⁺+1+NH₃, 100). Anal. Calcd forC₁₅H₁₆N₄O₉S₂: C, 39.13; H, 3.50; N, 12.17. Found: C, 39.46; H, 3.55; N,11.86.

To a stirred solution of 2a (10.28 g, 22.35 mmole) in acetone (300 mL)maintained at 020 C. was added dropwise a mixture of CrO₃ (5.82 g, 58.2mmole) in water (15 mL) containing concentrated sulfuric acid (6 mL).After the addition was complete, the reaction mixture was stirredvigorously at room temperature overnight and poured into ice-water.Solid was filtered, washed with water and dried. Compound 3a wasobtained as a white solid (9.31 g, 91%), which was recrystallized fromacetone and hexanes to give a colorless crystalline solid: mp 212° C.(dec). ¹H NMR (acetone-d₆): δ4.12 (d, J=5.50 Hz, 4 H), 7.19(t, 2 H),8.09 (d, J=9.16 Hz, 4 H), 8.39 (d, J=9.15 Hz, 4 H). ¹³C NMR (DMSO-d₆):δ49.1, 124.3, 127.9, 146.1, 149.4, 199.9. MS (CI/NH₃): m/z 476(M⁺+1+NH₃,100). Anal. Calcd for C₁₅H₁₄N₄O₉S₂: C, 39.30; H, 3.08; N,12.22. Found: C, 39.23; H, 3.03; N, 11.79.

A mixture of ketone 3a (12.29 g, 26.83 mmole), ethylene glycol (6.06 g,97.63 mmole), and p-toluenesulfonic acid monohydrate (˜0.5 g) in toluene(200 mL) was heated under reflux for 3 days using a Dean-Stark apparatusto remove water. After cooling, the solid was filtered, washed withwater and methylene chloride. Compound 4a was obtained as a light graysolid (12.12 g, 90%) that was recrystallized from DMF and water to givea colorless crystalline: mp 237° C. (dec). ¹H NMR (DMSO-d₆): δ2.99 (d,J=6.41 Hz, 4 H), 3.59 (s, 4 H), 7.99 (d, J=9.15 Hz, 4 H), 8.13 (t, 2 H),8.37 (d, J=8.84 Hz, 4 H). ¹³C NMR (DMSO-d₆): δ45.9, 65.0, 106.7, 124.2,127.8, 146.7, 149.3. MS (CI/NH₃): m/z 520 (M⁺+1+NH₃, 100). Anal. Calcdfor C₁₇H₁₈N₄O₁₀S₂: C, 40.64; H, 3.61; N, 11.15. Found: C, 40.63; H,3.44; N, 11.11.

To a refluxed solution of 4a (1.01 g, 2.01 mmole), potassium carbonate(0.72 g, 5.21 mmole) in acetone (50 mL) was added dropwise a solution of3-bromo-2-(bromomethyl)propene (0.46 g, 2.15 mmole) in acetone (20 mL)in 1 h. The resulting mixture was heated with stirring under refluxovernight and acetone was evaporated. After the residue was washed withwater and dried, a yellow solid was afforded which was recrystallizedfrom acetone and hexanes to give 5a as a colorless crystalline solid(0.85 g, 76%): mp 199-201° C. ¹H NMR (CDCl₃): δ3.42 (s, 4 H), 3.81 (s, 4H), 4.06 (s, 4 H), 5.22 (s, 2 H), 8.04 (d, J=9.16 Hz, 4 H), 8.38 (d,J=9.16 Hz, 4 H). ¹³C NMR (CDCl₃): δ53.1, 54.0, 65.3, 106.6, 120.9,124.4, 128.8, 140.0, 144.3, 150.3. MS (CI/NH₃): m/z 572 (M⁺+1+NH₃,100).Anal. Calcd for C₂₁H₂₂N₄O₁₀S₂: C, 45.48; H, 4.00; N, 10.10; S, 11.56.Found: C, 45.57; H, 4.02; N, 9.65; S, 11.31.

A mixture of ozone in oxygen was bubbled into a stirred solution of 5a(0.98 g, 1.77 mmole) in methylene chloride (100 mL) at −78° C. until thesolution turned to blue; then oxygen was continued to bubble into it toremove excess ozone. To the solution was added excess of methyl sulfide.Upon completion of the addition, the mixture was slowly warmed up toroom temperature. After stirred for 1 h, solvent was removed underreduced pressure. The residue was washed with water, filtered, washedwith water, acetone and dried to afford 6a as a white solid (0.94 g,95%): mp 244° C. (dec). ¹H NMR (DMSO-d₆): δ3.58 (s, 4 H), 3.92 ( d,J=2.74 Hz, 8 H), 8.10 (d, J=8.24 Hz, 4 H), 8.39 (d, J=9.16 Hz, 4 H). ¹³CNMR (DMSO-d₆): δ55.1, 64.8, 106.5, 124.7, 128.7, 142.9, 150.1, 202.3. MS(CI/NH₃): m/z 574 (M⁺+1+NH₃,100). Anal. Calcd for C₂₀H₂₀N₄O₁₁S₂: C,43.16; H, 3.62; N, 10.07; S, 11.52. Found: C, 42.95; H, 3.60; N, 9.83;S, 11.43.

A mixture of 6a (4.00 g, 7.19 mmole), sodium acetate (2.75 g, 33.52mmole), hydroxylamine hydrochloride (1.02 g, 14.68 mmole) in ethanol(200 mL) was heated with stirring under reflux for 24 h, then cooled toroom temperature and poured into ice-water. The precipitate wascollected by filtration and dried. A white solid was afforded (3.76 g,91%) which was recrystallized from acetone and hexanes to give 7a as acolorless crystalline: mp 213° C. ¹H NMR (DMSO-d₆): δ3.30 (s, 2 H), 3.58(s, 2 H), 3.83 (s, 2 H), 3.84 (s, 2 H), 4.01 (s, 2 H), 4.07 (s, 2 H),8.08 (dd, J=9.16 Hz, 2.75 Hz, 4 H), 8.38 (m, 4 H),11.3 (s, 1 H). ¹³C NMR(DMSO-d₆): δ45.0, 50.2, 54.0, 54.3, 64.5, 106.3, 124.3, 124.7, 128.5,142.8, 144.8, 149.7, 150.0, 152.1. MS (CI/NH₃): m/z 589 (M⁺+1+NH₃,100).Anal. Calcd for C₂₀H₂₁N₅O₁₁S₂: C, 42.03; H, 3.70; N, 12.25; S, 11.22.Found: C, 41.97; H, 3.75; N, 12.12; S, 11.35.

A suspension of 7a (1.75 g, 3.06 mmole) in methylene chloride (100 mL)was heated with stirring under reflux and a solution of 100% nitric acid(15 mL), ammonium nitrate (0.32 g, 4.00 mmole) and urea (0.23 g, 3.83mmole) in methylene chloride (50 mL) was added dropwise in 1 h. Uponcompletion of the addition, the reaction mixture was heated under refluxfor 1.5 h, cooled to 0° C., and then iced water (150 mL) was addedfollowed by removal of methylene chloride in a vacuum. The resultingmixture was filtered and a pale yellow solid was afforded. The driedsolid was stirred in acetone for 20 min and filtered to give a whitesolid which was identical with compound 6a (0.83 g, 49%). The filtratewas evaporated and the residue was washed with methylene chloride; 8awas afforded as a white solid (0.64 g, 33%) that was recrystallized fromacetone and hexanes to give a colorless crystalline: mp 258° C. (dec).¹H NMR (DMSO-d₆): δ3.45 (s, 4 H), 3.93 (s, 4 H), 4.58 (s, 4 H), 8.09 (d,J=8.24 Hz, 4 H), 8.44 (d, J=9.15 Hz, 4 H). ¹³C NMR (DMSO-d₆): δ50.2,55.5, 64.9, 105.7, 118.2, 124.8, 129.1, 141.2, 150.5. MS (CI/NH₃): m/z650 (M⁺+1+NH₃, 100). Anal. Calcd for C₂₀H₂₀ N ₆O₁₄S₂: C, 37.98; H, 3.19;N, 13.29. Found: C, 38.19; H, 3.15; N, 12.93.

Example 2 Preparation ofhexahydro-7,7-dinitro-1,5-bis(4-nitrobenzenesulfonyl)-1,5-diazocin-3(2H)-one(“Ns”=p-nitrobenzenesulfonyl)

A mixture of 8a (0.64 g, 1.01 mmole) and concentrated sulfuric acid (1mL) in methylene chloride (20 mL) was stirred at room temperature for 3days followed by addition of iced water (50 mL). The resulting mixturewas filtered and the solid was washed with water, acetone and dried,compound 9a was afforded as a white solid (0.55 g, 92%): mp 230° C.(dec). ¹H NMR (DMSO-d₆): δ4.29 (s, br, 4 H), 4.92 (s, br, 4 H), 8.14 (d,J=8.24 Hz, 4 H), 8.48 (d, J=8.24 Hz, 4 H). ¹³C NMR (DMSO-d₆): δ54.2,60.2, 120.3, 125.1, 129.3, 140.4, 150.7, 202.7. MS (CI/NH₃): m/z 606(M⁺+1+NH₃, 25). Anal. Calcd for C₁₈H₁₆N₆O₁₃S₂: C, 36.74; H, 2.74; N,14.28. Found: C, 36.80; H, 2.80; N, 13.80.

Example 3 Preparation of 3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(4-nitrobenzenesulfonyl)-1,5-diazocine

In a jacketed tube reactor, 2.0 mL of 30% fuming sulfuric acid plus 10mL of trichlorofluoromethane were cooled to −25° C., and 2.0 g ofdifluoramine was condensed into the mixture, which was then warmed to+10° C. (to melt the acid layer) and recooled to −15° C. Solidhexahydro-7,7-dinitro-1,5-bis(4-nitrobenzenesulfonyl)-1,5-diazocin-3(2H)-one(9a, 0.21 g, 0.36 mmol) was added via a solid addition funnel and thenwashed in with 10 mL trichlorofluoromethane. The mixture was stirred,sealed, at −15° C. for 3 hours and then poured onto ice; the reactor waswashed with dichloromethane and then water. The quenched mixture wasbasified with saturated aqueous sodium bicarbonate to reach a pH of 2,and then extracted with dichloromethane (4×100 mL). The solute wasredissolved in hot dichloromethane; chloroform was added; and themixture was concentrated by rotary evaporation. Precipitate from thedichloromethane-chloroform mixture was filtered off and then redissolvedin acetone. The remaining glassware was washed off with acetone, whichsolution was filtered through a medium-porosity glass frit. Acetonesolutions were collected and evaporated to dryness. To the solute wasadded 25 mL chloroform, 10 mL dichloromethane, and 5 mL acetone, and themixture was boiled. Dichloromethane was removed by rotary evaporation,and the precipitate was filtered off. The filtered solid as well as thesolid residue stuck to the recrystallization flask were dried in avacuum desiccator. The product was analyzed by NMR to be an acetoneadduct of 3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(4-nitrobenzenesulfonyl)-1,5-diazocine (0.2358 g); m.p. 208° C.(explodes). ¹H NMR (acetone-d₆): δ2.09 (s), 4.58 (s, br, 4 H), 4.76 (s,4 H), 8.31 (d, J=9.1 Hz, 4 H), 8.57 (d, J=9.1 Hz, 4 H). ¹H NMR(DMSO-d₆): δ2.09 (s), 4.47 (s, 4 H), 4.59 (s, br, 4 H), 8.19 (d, J=9.0Hz, 4 H), 8.51 (d, J=9.0 Hz, 4 H). ¹³C NMR (DMSO-d₆): δ30.7, 49.4, 52.9,97.8, 118.3, 125.2, 129.9, 140.3, 150.9. ¹⁹F NMR (acetone-d₆): δ29.9.

The acetone solvent adduct was dried in a vacuum oven at 50 -55° C. forthree days, producing pure bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(4-nitrobenzenesulfonyl)-1,5-diazocine (90% yield).¹H NMR (DMSO-d₆): δ4.47 (s, 4 H), 4.59 (s, br, 4 H), 8.18 (d, J=8.8 Hz,4 H), 8.51 (d, J=8.9 Hz, 4 H). ¹H NMR (CDCl ₃): δ4.18 (s, br, 4 H), 4.54(s, 4 H), 8.01 (d, J=9.0 Hz, 4 H), 8.48 (d, J=8.9 Hz, 4 H). ¹⁹F NMR(CDCl₃): δ29.3.

Example 4 Preparation ofhexahydro-7,7-dinitro-1,5-bis(2-nitrobenzenesulfonyl)-1,5-diazocin-3(2H)-oneethylene ketal (“Ns”=o-nitrobenzenesulfonyl)

To a stirred solution of 1 (2.38 g, 26.4 mmole) and potassium carbonate(9.35 g, 67.7 mmole) in water (100 mL) maintained at 0° C. was addedo-nosyl chloride (11.71 g, 52.8 mmole) in THF (50 mL) dropwise. Uponcompletion of the addition, the reaction mixture was stirred at roomtemperature overnight. Layers were separated and the aqueous layer wasextracted with ethyl acetate (2×50 ml). The combined organic layers werewashed with saturated aqueous sodium bicarbonate and brine and thendried over magnesium sulfate. Removal of solvent gave 2b as a paleyellow solid (9.67 g, 80%). Recrystallization from ethyl acetate andhexanes afforded a white solid: ¹H NMR (acetone-d₆): δ3.08 (m, 2 H),3.26 (m, 2 H), 3.89 (m, 1 H), 4.56 (d, J=5.49 Hz, 1 H), 6.56 (t, 2 H),7.92 (m, 6 H), 8.09 (m, 2 H). MS (CI/NH₃): m/z 478. Anal. Calcd forC₁₅H₁₆N₄O₉S₂: C, 39.13; H, 3.50; N, 12.17. Found: C, 38.99; H, 3.49; N,11.80.

To a stirred solution of 2b (0.48 g, 1.04 mmole) in acetone (20 mL)maintained at 0° C. was added dropwise a mixture of CrO₃ (0.30 g, 3.0mmole) in water (0.63 g) containing concentrated sulfuric acid (0.63 g).After the addition was complete, the reaction mixture was stirredvigorously at room temperature overnight and poured into ice-water.Solid was filtered, washed with water and dried. Compound 3b wasobtained as a white solid (0.43 g, 90%), which was recrystallized fromacetone and water to give a colorless crystalline solid: mp 165° C.(dec). ¹H NMR (acetone-d₆): δ4.23 (d, J=4.58 Hz, 4 H), 6.90 (t, 2 H),7.82-8.05 (m, 8 H). MS (CI/NH₃): m/z 476. Anal. Calcd for C₁₅H₁₄N₄O₉S₂:C, 39.30; H, 3.08; N, 12.22. Found: C, 39.25; H, 3.30; N, 12.14.

A mixture of ketone 3b (3.30 g, 7.21 mmole), ethylene glycol (1.50 g,24.17 mmole), and p-toluenesulfonic acid monohydrate (˜0.5 g) in benzene(150 mL) was heated under reflux for 3 days using a Dean-Stark apparatusto remove water. After cooling, the solvent was removed and the residuewas recrystallized from DMF and water. Compound 4b was obtained as acolorless crystalline (3.20 g, 89%): mp 195-197° C. ¹H NMR (acetone-d₆):δ3.35 (d, J=6.41 Hz, 4 H), 3.69 (s, 4 H), 6.56 (t, 2 H), 7.90 (m, 6 H),8.05 (m, 2 H). HRMS (FAB): Calc for C₁₇H₁₉N₄O₁₀S₂ (MH⁺) 503.0543, foundm/z 503.0546. Anal. Calcd for: C₁₇H₁₈N₄O₁₀S₂ C, 40.64; H, 3.61; N,11.15. Found: C, 40.67;H, 3.63; N, 11.00.

To a refluxed solution of 4b (0.54 g, 1.08 mmole), potassium carbonate(0.43 g, 3.11 mmole) in acetone (50 mL) was added dropwise a solution of3-bromo-2-(bromomethyl)propene (0.23 g, 1.07 mmole) in acetone (30 mL)in 1 h. The resulting mixture was heated with stirring under refluxovernight and acetone was evaporated. The residue was dissolved inmethylene chloride washed with water and dried over magnesium sulfate.Removal of solvent gave a pale yellow solid (0.51 g, 86%). The crudeproduct was purified by passing through silica gel, eluting with ethylacetate and hexanes, and the resulting solid was recrystallized fromethyl acetate and hexanes, affording a colorless crystalline solid, 5b:mp 150-151° C. ¹H NMR (CDCl₃): δ3.55 (s, 4 H), 4.01 (s, 8 H), 5.26 (s, 2H), 7.70 (m, 6 H), 8.02 (m, 2 H).

A mixture of ozone in oxygen was bubbled into a stirred solution of 5b(3.26 g, 5.88 mmole) in methylene chloride (250 mL) at −78° C. until thesolution turned blue; then oxygen was bubbled into it to remove excessozone. To the solution was added excess dimethyl sulfide. Uponcompletion of the addition, the mixture was slowly warmed up to roomtemperature. After stirring for 1 h, solvent was removed under reducedpressure; 6b was obtained as a white solid (3.20 g, 98%) which wasrecrystallized from methylene chloride and hexanes to give a colorlesscrystalline solid: mp 219° C. (dec). ¹H NMR (DMSO-d₆): δ3.67 (s, 4 H),3.94 (s, 4 H), 4.06 (s, 4 H), 7.90 (m, 4 H), 8.04 (m, 4 H). HRMS (FAB):Calc for C₂₀H₂₁N₄O₁₁S₂: (MH⁺) 557.0648, found m/z 557.0652.

A mixture of 6b (2.14 g, 3.85 mmole), sodium acetate (1.97 g, 24.00mmole), and hydroxylamine hydrochloride (0.54 g, 7.77 mmole) in ethanol(200 mL) was heated with stirring under reflux for 48 h, and then cooledto room temperature and poured into ice-water. The precipitate wascollected by filtration and dried. A white solid was afforded (2.13 g,97%), which was recrystallized from acetone and hexanes to give 7b as acolorless crystalline solid: mp 220° C. (dec). ¹H NMR (acetone-d₆):δ3.56 (s, 2 H), 3.70 (s, 2 H), 3.97 (s, 4 H), 4.19 (s, 2 H), 4.45 (s, 2H), 7.92 (m, 6 H), 8.11 (m, 2 H), 10.51 (s, 1 H). HRMS (FAB): Calc forC₂₀H₂₂N₅O₁₁S₂: (MH⁺) 572.0757, found m/z 572.0749. Anal. Calcd forC₂₀H₂₁N₅O₁₁S₂: C, 42.03; H, 3.70; N, 12.25; S, 11.22. Found: C, 42.12;H, 3.91; N, 12.17; S, 11.03.

A suspension of 7b (0.39 g, 0.68 mmole) in methylene chloride (30 mL)was heated with stirring under reflux, and a solution of 100% nitricacid (5 mL), ammonium nitrate (81 mg, 0.96 mmole) and urea (82 mg, 1.37mmole) in methylene chloride (15 mL) was added dropwise over 1 h. Uponcompletion of the addition, the reaction mixture was heated under refluxfor 2 h, cooled to room temperature, washed with water, aqueous sodiumbicarbonate, brine and dried over magnesium sulfate. Removal of solventproduced a white solid. The dried solid was stirred in methylenechloride for 20 min and filtered to give 8b as a white solid (0.20 g,46%), which was recrystallized from DMF and water to afford a colorlesscrystalline solid: mp 245° C. (dec). ¹H NMR (DMSO-d₆): δ3.57 (s, 4 H),3.90 (s, 4 H), 4.83 (s, 4 H), 7.87-8.10 (m, 8 H). ¹³C NMR (DMSO-d₆):δ50.3, 55.3, 64.9, 105.4, 118.2, 124.8, 128.7, 130.0, 132.9, 135.5,147.9. The filtrate was concentrated; a white solid was obtained whichwas identical with 6b (0.16 g, 42%).

Example 5 Preparation ofhexahydro-7,7-dinitro-1,5-bis(2-nitrobenzenesulfonyl)-1,5-diazocin-3(2H)-one(“Ns”=o-nitrobenzenesulfonyl)

A mixture of 8b (0.80 g, 1.27 mmole) and concentrated sulfuric acid (1mL) in methylene chloride (20 mL) was stirred at room temperature for 3days, followed by addition of ice-water (50 mL). The resulting mixturewas filtered, and the solid was washed with water and dried; compound 9bwas afforded as a white solid (0.65 g, 87%). ¹H NMR (acetone-d₆): δ4.47(s, 4 H), 5.24 (s, 4 H), 8.06 (m, 8 H). ¹³C NMR (DMSO-d₆): δ54.9, 60.2,120.5, 125.7, 128.1, 129.7, 133.6, 136.1, 148.0, 202.6.

Example 6 Preparation of3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(2-nitrobenzenesulfonyl)-1,5-diazocine

By a procedure similar to that of Example 3, difluoramination of 0.20 ghexahydro-7,7-dinitro-1,5-bis(2-nitrobenzenesulfonyl)-1,5-diazocin-3(2H)-one (9b) produced 0.1495 g (65% yield) of pure3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(2-nitrobenzenesulfonyl)-1,5-diazocineafter recrystallization from acetone-chloroform; m.p. 225-228° C. (dec).¹H NMR (acetone-d₆): δ4.67 (s, br, 4 H), 5.02 (s, 4 H), 8.01-8.21 (m, 8H). ¹³C NMR (acetone-d₆): δ50.6 (quintet, J=7.0 Hz), 53.7, 98.0 (m),118.9, 126.3, 129.5, 132.4, 134.0, 137.3, 149.6. ¹⁹FNMR (acetone -d₆):δ629.3.

Example 7 Preparation of3,3-bis(difluoramino)octahydro-1,5,7,7-dinitro-1,5-diazocine (TNFX)

To 10 mL of triflic acid was added 1.0 mL of 98-100% nitric acid atambient temperature, and the mixture was stirred for 1 hour. To thismixture cooled in an ice-water bath was slowly added solid3,3-bis(difluoramino)octahydro-7,7-dinitro-1,5-bis(4-nitrobenzenesulfonyl)-1,5-diazocine(49.6 mg) via a solid addition funnel. The resulting suspension waswarmed to 55° C. in an oil bath. After recooling in an ice-water bath,another 1.0 mL nitric acid was added, and the mixture was rewarmed to55° C. Another 10 mL triflic acid was added dropwise, and the mixturewas stirred at 55° C. overnight. Additional triflic acid was addeddropwise to make a total of 40 mL of solution, and the solution wasstored in an oven at 55° C. After 14 days, one-fourth of the reactionsolution was separated, and to this portion was added ˜10% by volume ofantimony pentafluoride. After two days of storage of this solution atroom temperature, most of the triflic acid was vacuum-distilled at 55°C.; the residue was quenched onto ice-water, neutralized to pH 7 withaqueous sodium carbonate, and extracted with dichloromethane.Chromatography of the solute (silica gel, chloroform-dichloromethane)separated 3,3-bis(difluoramino)octahydro-1,5,7,7-dinitro-1,5-diazocine(TNFX) from by-products, and its identity was confirmed by X-raycrystallography. ¹H NMR (acetone-d₆): δ5.14 (s, br, 4 H), 5.50 (s, 4 H).¹⁹F NMR (acetone-d₆): δ29.7.

Although the description above contains many specificities, these shouldnot be construed as limiting the scope of the invention but as merelyproviding an illustration of the presently preferred embodiment of theinvention. Thus the appended claims and their legal equivalents shoulddetermine the scope of this invention.

What is claimed is:
 1. A compound having the formula

wherein Ns is selected from the group consisting of halosulfonyl, aregioisomer of fluoroarenesulfonyl, polyhaloalkanesulfonyl,polyhaloarenesulfonyl, a regioisomer of cyanoarenesulfonyl,polycyanoarenesulfonyl, a regioisomer of nitroarenesulfonyl, andpolynitroarenesulfonyl.
 2. The compound of claim 1 wherein saidregioisomer of fluoroarenesulfonyl is selected from the group consistingof 2-,3- and 4-fluoro-substituted arenesulfonyl, wherein saidregioisomer of cyanoarenesulfonyl is selected from the group consistingof 2-,3- and 4-cyano-substituted arenesulfonyl and wherein saidregioisomer of nitroarenesulfonyl is selected from the group consistingof 2-,3- and 4-nitro-substituted arenesulfonyl.
 3. A compound having theformula

wherein Ns is selected from the group consisting of halosulfonyl, aregioisomer of fluoroarenesulfonyl, polyhaloalkanesulfonyl,polyhaloarenesulfonyl, a regioisomer of cyanoarenesulfonyl,polycyanoarenesulfonyl, a regioisomer of nitroarenesulfonyl, andpolynitroarenesulfonyl.
 4. The compound of claim 3 wherein saidregioisomer of fluoroarenesulfonyl is selected from the group consistingof 2-,3- and 4-fluoro-substituted arenesulfonyl, wherein saidregioisomer of cyanoarenesulfonyl is selected from the group consistingof 2-,3- and 4-cyano-substituted arenesulfonyl and wherein saidregioisomer of nitroarenesulfonyl is selected from the group consistingof 2-,3- and 4-nitro-substituted arenesulfonyl.
 5. A compound having theformula

wherein Ns is selected from the group consisting of halosulfonyl, aregioisomer of fluoroarenesulfonyl, polyhaloalkanesulfonyl,polyhaloarenesulfonyl, a regioisomer of cyanoarenesulfonyl,polycyanoarenesulfonyl, a regioisomer of nitroarenesulfonyl, andpolynitroarenesulfonyl.
 6. The compound of claim 5 wherein saidregioisomer of fluoroarenesulfonyl is selected from the group consistingof 2-,3- and 4-fluoro-substituted arenesulfonyl, wherein saidregioisomer of cyanoarenesulfonyl is selected from the group consistingof 2-,3- and 4-cyano-substituted arenesulfonyl and wherein saidregioisomer of nitroarenesulfonyl is selected from the group consistingof 2-,3- and 4-nitro-substituted arenesulfonyl.